Stress‐inducible phosphoprotein 1 (Sti1/Stip1/Hop) sequesters misfolded proteins during stress
Bibliographic record
Abstract
Co-chaperones are key elements of cellular protein quality control. They cooperate with the major heat shock proteins Hsp70 and Hsp90 in folding proteins and preventing the toxic accumulation of misfolded proteins upon exposure to stress. Hsp90 interacts with the co-chaperone stress-inducible phosphoprotein 1 (Sti1/Stip1/Hop) and activator of Hsp90 ATPase protein 1 (Aha1) among many others. Sti1 and Aha1 control the ATPase activity of Hsp90, but Sti1 also facilitates the transfer of client proteins from Hsp70 to Hsp90, thus connecting these two major branches of protein quality control. We find that misbalanced expression of Sti1 and Aha1 in yeast and mammalian cells causes severe growth defects. Also, deletion of STI1 causes an accumulation of soluble misfolded ubiquitinated proteins and a strong activation of the heat shock response. We discover that, during proteostatic stress, Sti1 forms cytoplasmic inclusions in yeast and mammalian cells that overlap with misfolded proteins. Our work indicates a key role of Sti1 in proteostasis independent of its Hsp90 ATPase regulatory functions by sequestering misfolded proteins during stress.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".